Is the preoperative use of amphetamine drugs and their potential interaction with general anesthetics a clinical concern? Prescription amphetamine drugs are used legitimately for several medical and psychological indications, including attention deficit hyperactivity disorder in children and adults, narcolepsy, exogenous obesity appetite suppression, psychotherapeutic indications such as depression, and even for Parkinson’s disease (1–3). Although we do not have specific figures, the use of chronic amphetamine drugs may have increased in the past several years as new drugs have been approved and the scope of indications has broadened.
We previously raised the question of whether it is indicated to discontinue long-term prescription amphetamine therapy before general anesthesia (4). Current anesthesia textbooks frequently reference original articles written more than 25 yr ago (5,6) that list the biochemical concerns and potential adverse outcomes but that are based on very limited clinical data. The current report attempts to further clarify and demonstrate a trend of safety in general anesthesia for these patients in whom discontinuing amphetamine therapy could have significant adverse effects on their physical or emotional stability.
We prospectively evaluated eight patients taking therapeutic doses of prescribed amphetamines and undergoing a variety of surgical procedures. Patients were prescribed amphetamines predominately for psychiatric and neurological purposes. Their ages ranged from 22 to 77 yr and 4 of the 8 patients were female (Table 1).
As per the protocol of our preoperative evaluation clinic (7), all patients were requested to take their usual medications in a sip of water on the day of surgery. This included prescription amphetamines. No patients with a history of prescription amphetamine use had surgery cancelled or postponed. All patients were taking their medications as prescribed within ranges customary for their diagnosis. Patients’ other concurrent medications included antibiotics (cephalexin, sulfamethoxazole/trimethoprim), antidepressants (sertraline, bupropion, escitalopram, paroxetine), analgesics (hydrocodone, oxycodone), anxiolytics (buspirone), cardiac (digoxin) and gabapentin, warfarin, valsartan, atorvastatin, and allopurinol. We believe that none of these medications had an influence on this study or the outcome.
The assigned anesthesiologist was informed that the patient was taking an amphetamine prescription and would continue this medication until the time of surgery. Purposefully, there was no discussion to suggest or alter the assigned anesthesiologist’s plan of perioperative management, including choice of drugs or technique. Review of each patient’s intraoperative anesthesia record showed no modified anesthesia management based on prescription amphetamine use. The preoperative evaluation of the patients taking prescription amphetamine was not modified, except that all patients did have a baseline electrocardiogram. A detailed history of the prescription usage was elicited to determine if the patient had exceeded prescribed dosing. It was also determined that each patient in the study was not abusing or using elicit drugs concurrently. All anesthesiologists used their usual and customary anesthesia drugs and techniques (Table 2). Six of the 8 patients were tracheally intubated, of whom 5 had ventilation controlled and one had spontaneous ventilation. Two patients breathed spontaneous by via a mask. Five of the eight patients had arterial blood pressure monitoring secondary to the scope of the surgical case, medical history, and potential for blood loss (Table 1).
Baseline arterial blood pressure and heart rate appeared stable and within normal limits for all patients in the 10 min before induction. Anesthesia was induced with thiopental, propofol, or etomidate. During induction, each patient’s mean arterial blood pressure decreased appropriately within 10%–20% of the baseline value taken before induction. No patient experienced hypotension or hypertension at induction or intraoperatively outside of the recognized standards (Table 2). Estimated blood loss in 3 of the patients was between 20 mL–40 mL; 4 patients had blood loss between 200 mL–900 mL and one patient had blood loss of 1800 mL. No patient received an intraoperative blood transfusion but all received appropriate crystalloid IV replacement for blood loss.
During the surgical procedures that ranged from 30 min to 4.25 h, all patients maintained hemodynamic stability. No patient required a vasopressor or any form of hemodynamic intervention. At the conclusion of surgery and anesthesia, all patients were taken to the postanesthesia care unit (PACU), where they were monitored closely. Patients remained in the PACU between 2–3 h, and 7 of 8 patients were admitted to the hospital as planned postoperatively. Three of 8 patients had minimal pain, 3 patients had moderate pain, and 2 had significant pain postoperatively in the PACU. As appropriate, patients were given narcotic pain relief at customary and appropriate intervals. No hypotension or significant changes in the patients’ hemodynamic stability were observed in the PACU when the patients experienced postoperative pain or narcotic pain relief (Table 2).
The patients’ hospital stays ranged from 1 day to 8 days, and all patients were maintained on their customary preoperative medications, including their amphetamine drug. There was no postoperative hemodynamic instability or adverse events for any patient during hospitalization.
We report here our experience of prospectively evaluating eight patients undergoing general anesthesia while taking prescription amphetamine drugs on a chronic basis.
Amphetamines are non-catecholamine, sympathetic amines with powerful central nervous system stimulation activity. Peripheral actions can include an increase of systolic and diastolic blood pressure and a weak bronchodilator and respiratory stimulant action. The central nervous system action of amphetamines appears associated with the local release of biogenic amines such as norepinephrine from nerve terminal storage sites (8).
It is reported that chronic amphetamine exposure and stimulation of the adrenergic and peripheral nerve terminals causes a depletion of catecholamine receptor storage (9). This reduction in reserve catecholamines, especially norepinephrine, is thought to contribute to a blunted physiologic and sympathetic response to hypotension, as may occur in anesthesia. Intraoperative, refractory hypotension or bradycardia in patients taking amphetamines should be treated with direct-acting vasopressors, such as epinephrine (IV, 10–100 μg) or phenylephrine (IV, 50–100 μg). Ephedrine, often a first choice drug for intraoperative hypotension, has been reported to have a diminished or absent pressor response after chronic amphetamine use (6).
There is little in the anesthesia literature concerning clinical intraoperative experience of patients taking chronic amphetamines. A single 1979 case report (5) of a cardiac arrest and death during a cesarean delivery in a chronic amphetamine abuser has often been referenced in the literature as demonstrating cardiovascular instability and a possible outcome in these patients. The authors (5) admit that it was difficult to prove the association of the patient’s amphetamine use with her intraoperative death secondary to several other concurrent clinical factors. However, this case report has fostered references in several anesthesia texts and contributes to the belief that discontinuation of amphetamine drugs before surgery could increase patient safety and reduce the chances of a catastrophic intraoperative event.
In 2000 we reported (4) the results of a 61-year-old man who underwent anesthesia and surgery for a bowel obstruction and who had being taking dextroamphetamine for more than 40 years because of severe narcolepsy. He remained hemodynamically stable throughout the anesthetic and postoperatively and was discharged home uneventfully.
In this present report of eight additional cases in which the amphetamine drug was not stopped preoperatively, the general anesthesia proceeded successfully without any cardiovascular instability in all patients. No dramatic fluctuations in arterial blood pressure were observed at induction or during the course of the surgeries.
We cannot conclude from these evaluations that patients taking nonprescription amphetamines, such as in substance abuse, will have the same outcome of cardiac, hemodynamic stability intraoperatively. As a follow-up to these cases of patients taking chronic prescription amphetamines, we are in the process of evaluating substance abuse patients for anesthesia and surgery who take amphetamines at very large dose levels.
The outcomes of this study are based on the data from 8 patients. The conclusions suggest potential stable anesthesia management in patients receiving chronic prescription amphetamines. We believe a larger patient study population would conclude similar findings. However, until a study is concluded, we recommend that direct-acting vasopressors, including phenylephrine or epinephrine, should be readily available intraoperatively. In the eight cases we evaluated, no patient required any vasopressor drugs.
In 2000 we indicated the importance of evaluating a series of these patients taking chronic amphetamine therapy for anesthesia intraoperative outcome. With these additional eight patients, we believe that the anesthesiologist may not need to discontinue chronic amphetamine therapy before elective surgeries.
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